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Background In adults with moderate renal impairment (creatinine clearance [CrCl] 30–50 mL/min) undergoing total hip or knee replacement (THR/TKR), the recommended dose of dabigatran etexilate is 150 mg once daily (qd). We investigated the steady state pharmacokinetics, pharmacodynamics and safety in these patients. Methods Single-arm, open-label phase 4 study ( NCT01184989 ) in Caucasian patients receiving dabigatran etexilate 75 mg 1–4 h after surgery and 150 mg qd on days 2–10 (TKR) or days 2–35 (THR). Plasma total dabigatran concentrations (day 6 ± 1) were determined by high-performance liquid chromatography tandem mass spectrometry and indirectly using the commercially available diluted thrombin time (dTT) assay (Hemoclot® Thrombin Inhibitors). Results Of 112 patients (mean CrCl 42.5 mL/min, age 79.1 years, 69.6% female), 100 completed the study. Geometric mean trough and peak dabigatran concentrations were 47.5 ng/mL (10th–90th percentile 19.7–120) and 166 ng/mL (49.1–364), respectively. There were four major bleeding events and no venous thromboembolic events. Dabigatran concentrations determined from dTT (and falling within the assay range of 50–500 ng/mL) underestimated actual values by 7.6% (90% confidence interval 5.3, 9.9), which is within the acceptance limits of ± 15%. Conclusions These findings in Caucasians with moderate renal impairment undergoing THR or TKR support the use of the 150 mg qd dose of dabigatran etexilate. With adequate set-up, calibration and quality control the dTT assay might be appropriate for situations, such as serious bleeding or a need for urgent surgery, where determination of dabigatran levels would be helpful. [ABSTRACT FROM AUTHOR]

Background: The importance of laminar airflow systems in operating rooms as protection from surgical site infections has been questioned. The aim of our study was to explore the differences in air contamination rates between displacement ventilation and laminar airflow systems during planned and acute orthopedic implant surgery. A second aim was to compare the influence of the number of people present, the reasons for traffic flow, and the door-opening rates between the 2 systems. Methods: Active air sampling and observations were made during 63 orthopedic implant operations. Results: The laminar airflow system resulted in a reduction of 89% in colony forming units in comparison with the displacement system (P < .001). The air samples taken in the preparation rooms showed high levels of bacterial growth (≈ 40 CFU/m3). Conclusions: Our study shows that laminar airflow-ventilated operating rooms offer high-quality air during surgery, with very low levels of colony forming units close to the surgical wound. The continuous maintenance of laminar air flow and other technical systems are crucial, because minor failures in complex systems like those in operating rooms can result in a detrimental effect on air quality and jeopardize the safety of patients. The technical ventilation solutions are important, but they do not guarantee clean air, because many other factors, such as the organization of the work and staff behavior, influence air cleanliness. [Copyright &y& Elsevier]

The direct thrombin inhibitor, dabigatran, and the selective factor Xa inhibitors, rivaroxaban and apixaban, are new oral anticoagulants that are approved in many countries for prevention of venous thromboembolism in patients undergoing elective hip or knee arthroplasty. All have a rapid onset of action, a low potential for food and drug interactions and a predictable anticoagulant effect that obviates the need for routine coagulation monitoring. These agents offer a convenient alternative to conventional anticoagulant drug regimens, including parenteral low-molecular-weight heparins and fondaparinux, and oral adjusted-dose vitamin K antagonists, for the prevention of venous thromboembolism in this surgical setting. This review summarizes the pharmacology, clinical trial results, bleeding risk and practical use of these new oral anticoagulants in clinical orthopaedic practice. Potential issues to be considered when using these oral anticoagulants include renal impairment, potential drug interactions, neuraxial anaesthesia and management of bleeding. [Copyright &y& Elsevier]

Abstract: Introduction: Oral thromboprophylaxis with dabigatran etexilate should be initiated as a half dose 1 to 4h after major orthopaedic surgery. However, a delay in dosing could occur for clinical or logistical reasons. A post hoc analysis was carried out to determine if patients with delayed dosing received adequate anticoagulation. Patients and methods: The RE-MODEL™ and RE-NOVATE® trials compared 220mg and 150mg dabigatran etexilate with 40mg enoxaparin. Pooled data for major venous thromboembolism (VTE) and VTE-related mortality (efficacy outcome) and major bleeding events (MBE), MBE/clinically relevant bleeding events, and all bleeding events (safety outcomes) were analysed. Results in patients with dosing delayed more than 4h postsurgery were compared with those of patients without a delay. Results: Onset of treatment was delayed in 724 (13.3%) of 5425 patients. Efficacy of 220mg dabigatran etexilate was similar in patients without delayed dosing, patients with a delay and patients with a delay until the day after surgery. Rates of efficacy outcome were higher in patients on 150mg dabigatran etexilate, but more than 80% of these patients were undertreated based on age or renal clearance status. Some differences in bleeding events were seen among patient groups by treatment arm. Conclusion: Dabigatran etexilate thromboprophylaxis should be initiated 1 to 4h postsurgery. Results from our post-hoc analysis indicate that no loss of efficacy appears to occur if initiation of dabigatran etexilate 220mg needs to be delayed. [Copyright &y& Elsevier]

Background: Understanding the protective potential of operating room (OR) ventilation under different conditions is crucial to optimizing the surgical environment. This study investigated the air quality, expressed as colony-forming units (CFU)/m3, during orthopedic trauma surgery in a displacement-ventilated OR; explored how traffic flow and the number of persons present in the OR affects the air contamination rate in the vicinity of surgical wounds; and identified reasons for door openings in the OR. Methods: Data collection, consisting of active air sampling and observations, was performed during 30 orthopedic procedures. Results: In 52 of the 91 air samples collected (57%), the CFU/m3 values exceeded the recommended level of <10 CFU/m3. In addition, the data showed a strongly positive correlation between the total CFU/m3 per operation and total traffic flow per operation (r = 0.74; P = .001; n = 24), after controlling for duration of surgery. A weaker, yet still positive correlation between CFU/m3 and the number of persons present in the OR (r = 0.22; P = .04; n = 82) was also found. Traffic flow, number of persons present, and duration of surgery explained 68% of the variance in total CFU/m3 (P = .001). Conclusions: Traffic flow has a strong negative impact on the OR environment. The results of this study support interventions aimed at preventing surgical site infections by reducing traffic flow in the OR. [Copyright &y& Elsevier]

Abstract: Introduction: Several anticoagulants have been associated with a ‘rebound effect’ that potentially increases the risk of thrombosis and cardiovascular events following discontinuation. Four Phase 3 trials of dabigatran etexilate in major orthopedic surgery incorporated measures to assess the risk of acute coronary syndrome (ACS) events during and after treatment. Materials and methods: Patients in RE-MOBILIZE®, RE-MODEL™, RE-NOVATE®, and RENOVATE® II were randomized to dabigatran etexilate (150mg or 220mg once daily) or enoxaparin for 6–35days, and followed for up to 90days. ACS data were tabulated from investigator-reported serious adverse events using ACS-specific Medical Dictionary for Regulatory Authorities (MedDRA) lower-level terms. To ensure that all ACS events were identified in the initial three studies, RE-MOBILIZE®, RE-MODEL™, and RE-NOVATE®, a broader list of MedDRA terms was prespecified that would trigger treatment-blinded adjudication. Results: When pooling the four trials, patients receiving dabigatran etexilate 220mg had the fewest treatment-emergent, investigator-reported ACS events (6 [0.16%] vs 14 [0.51%] for dabigatran 150mg and 13 [0.35%] for enoxaparin). Corresponding post-treatment rates were 2 (0.06%), 1 (0.04%), and 4 (0.11%). Similarly, treatment-emergent centrally adjudicated definite or likely ACS events in the first three trials were fewer in patients on dabigatran 220mg (16 [0.60%]) than dabigatran 150mg (26 [0.95%]) and enoxaparin (20 [0.74%]). The corresponding numbers post treatment were 2, 2, and 7. None of these between-group differences were statistically significant. Conclusion: No increased ACS signal was detected with dabigatran etexilate compared with enoxaparin during or after treatment. [Copyright &y& Elsevier]

Abstract: Introduction: The RECORD programme compared oral rivaroxaban with enoxaparin for prevention of venous thromboembolism after elective total hip or knee replacement. This analysis compared the safety of concomitant use of specified medications with rivaroxaban and enoxaparin by evaluating postoperative bleeding rates from the pooled RECORD1–4 data. Materials and methods: The co-medications were non-steroidal anti-inflammatory drugs and platelet function inhibitors, including acetylsalicylic acid (no dose restriction). The endpoints evaluated were the composite of major and non-major clinically relevant bleeding and any bleeding occurring after first oral study drug intake. The time relative to surgery was stratified into three time periods: day 1–3, day 4–7 and after day 7. Relative bleeding rate ratios for co-medication use versus non-use were derived using stratified Mantel–Haenszel methods and compared between rivaroxaban and enoxaparin groups. Results: Co-medication use with rivaroxaban or enoxaparin resulted in non-significant increases in bleeding events. Respective rate ratios were not significantly different between rivaroxaban and enoxaparin for all bleeding endpoints with concomitant use of non-steroidal anti-inflammatory drugs (any bleeding, 1.22 vs 1.22; major and non-major clinically relevant bleeding, 1.28 vs 0.90) and with concomitant use of platelet function inhibitors/acetylsalicylic acid (any bleeding, 1.32 vs 1.40; major and non-major clinically relevant bleeding, 1.11 vs 1.13). Conclusions: This explorative analysis indicates that there is no significant increase in bleeding risk for rivaroxaban compared with enoxaparin when co-administered with non-steroidal anti-inflammatory drugs or acetylsalicylic acid, although, because of low usage, the experience with platelet function inhibitors (except acetylsalicylic acid) was limited. [Copyright &y& Elsevier]

Abstract: We have characterized the mouse carotid body (CB) with special attention to nicotinic, purinergic and dopaminergic receptors as well as the TASK-1 K+-channel. Mouse CB sections were stained immunohistochemically and visualized using fluorescent and confocal microscopy. The CB type 1 cells contained the α3 (n =8), α4 (n =7), α7 (n =4) and β2 (n =3) nicotinic acetylcholine receptor (nAChR) subunits, the ATP-receptors P2X2 (n =15) and P2X3 (n =9), the dopamine D2 receptor (n =9) and the TASK-1 K+-channel (n =7). Here we report the presence of α3, α4, α7 and β2 nAChR subunits, the D2 receptor and the TASK-1 K+-channel in the mouse CB. Also, we confirm the presence of the P2X2 and P2X3 receptors in mouse CB. Thus, we have localized nicotinergic, purinergic and dopaminergic receptors and the TASK-1 K+-channel on a protein level in one species. Our data are in line with the theory that the CB chemoreceptor cell hosts an orchestra of receptor systems that ultimately modulate the response to hypoxia. [Copyright &y& Elsevier]

Background: Levosimendan is a compound with vasodilatory and inotropic properties. Experimental data suggest effective reversal of stunning and cardioprotective properties. Methods: This prospective, randomized, placebo-controlled, double-blind study included 60 patients with 3-vessel coronary disease and left ventricular ejection fraction (LVEF) of less than 0.50. Levosimendan administration (12 μg/kg bolus, followed by an infusion of 0.2 μg/kg/min) was started immediately after induction anesthesia. Predefined strict hemodynamic criteria were used to assess the success of weaning. If weaning was not successful, CPB was reinstituted and an epinephrine infusion was started. If the second weaning attempt failed, intraaortic balloon pumping (IABP) was instituted. Results: The groups had comparable demographics. The mean (standard deviation) preoperative LVEF was 0.36 (0.8) in both groups. The baseline cardiac index was 1.8 (0.3) L/min/m2 in the levosimendan group and 1.9 (0.4) L/min/m2 in the placebo group. The mean duration of CPB to primary weaning attempt was 104 (25) minutes in the levosimendan and 109 (22) minutes in the placebo group. Primary weaning was successful in 22 patients (73%) in the levosimendan group and in 10 (33%) in the placebo group (p = 0.002). The odds ratio for failure in primary weaning was 0.182 (95% confidence interval, 0.060 to 0.552). Four patients in the placebo group failed the second weaning and underwent IABP compared with none in the levosimendan group (p = 0.112). Conclusions: Levosimendan significantly enhanced primary weaning from CPB compared with placebo in patients undergoing 3-vessel on-pump coronary artery bypass grafting. The need for additional inotropic or mechanical therapy was decreased. [Copyright &y& Elsevier]

Abstract: Introduction: Rivaroxaban (BAY 59-7939) is a novel, oral, direct Factor Xa inhibitor in clinical development for the prevention of thromboembolic disorders. The aim of this study was to demonstrate proof-of-principle for rivaroxaban. Materials and methods: This was an open-label, dose-escalation study to assess the efficacy and safety of rivaroxaban, relative to enoxaparin, for the prevention of venous thromboembolism (VTE) after total hip replacement surgery. Patients were randomized in a 3:1 ratio to rivaroxaban (2.5, 5, 10, 20 and 30 mg twice daily [bid] or 30 mg once daily [od] starting 6–8 h after surgery) or enoxaparin (40 mg od starting the evening before surgery). Therapy continued until mandatory bilateral venography was performed 5–9 days after surgery. Results: A total of 625 patients received therapy, of whom 466 patients were eligible for the per-protocol efficacy analysis. The primary efficacy endpoint – deep vein thrombosis (DVT), pulmonary embolism (PE) or all-cause mortality – occurred in 22.2%, 23.8%, 20.0%, 10.2%, 17.4%, 15.1% and 16.8% of patients receiving rivaroxaban 2.5, 5, 10, 20, 30 mg bid, 30 mg od and enoxaparin, respectively. The dose-response relationship with rivaroxaban for the primary efficacy endpoint was not statistically significant (p =0.0504), although major VTE (proximal DVT, PE and VTE-related death) decreased dose dependently with rivaroxaban (p =0.0108). Major, post-operative bleeding increased dose dependently with rivaroxaban (p =0.0008), occurring in 0–10.8% of patients, compared with 0% in patients receiving enoxaparin. Conclusions: This study demonstrated proof-of-principle for rivaroxaban for the prevention of VTE after total hip replacement surgery. [Copyright &y& Elsevier]

The first clinical studies evaluating the safety and efficacy of melagatran, a novel, direct thrombin inhibitor, given subcutaneously as prophylaxis for venous thromboembolism (VTE) following total hip (THR) or total knee replacement (TKR) are reported. In Study I, 66 patients received subcutaneous melagatran (1.5–6 mg bid) in a poloxamer depot formulation, and in Study II, 104 patients received subcutaneous melagatran (2–4 mg bid) in saline or as a depot formulation in cyclodextrin. Treatment was given for 8–11 days, with the first dose administered immediately before surgery. Deep vein thrombosis (DVT) was assessed using mandatory bilateral venography on the last day of treatment, and pulmonary scintigraphy was performed if required. Bleeding complications occurred in the only patient who received melagatran 6 mg, and this dose-arm was discontinued. The frequency of VTE was low (12/129=9%, 95% confidence interval [CI]: 5–16%). Eight patients (6%) had distal DVT, three (2%) had proximal DVT, and in one patient (1%) pulmonary embolism (PE) was verified. In conclusion, subcutaneous melagatran 1.5–4.5 mg bid in saline or depot formulation was well tolerated and resulted in a low frequency of VTE. [Copyright &y& Elsevier]

Abstract: Introduction: Three pivotal phase 3 trials have demonstrated that oral dabigatran etexilate showed similar safety and efficacy to enoxaparin 40mg once daily (qd) for venous thromboembolism (VTE) prevention in patients undergoing total knee or hip replacement. Obesity is an established independent risk factor for VTE. Methods: A post-hoc pooled analysis of the three trials was performed to evaluate the safety and efficacy of dabigatran 220mg qd versus enoxaparin 40mg qd in patients with a normal body mass index (BMI) of >20–25kg/m2, pre-obese patients (BMI >25–30kg/m2) and obese patients (BMI >30kg/m2). The primary efficacy endpoint was major VTE and VTE-related mortality; safety endpoints included major, clinically relevant, or any bleeding events. Results: The mean BMIs for patients in the dabigatran and enoxaparin arms from all three trials, separately, were between 27.5 and 29.9kg/m2. Of the participants, 1417 (24.9%) had a normal BMI, 2373 (41.7%) were pre-obese and 1826 (32.1%) obese. In patients with normal BMI, the rates of the primary efficacy endpoint were significantly lower in the dabigatran than in the enoxaparin group (2.1% versus 4.3%; OR 0.48; 95% CI 0.24–0.97, P =0.037). No significant difference between dabigatran and enoxaparin in the primary efficacy endpoint was observed in the other subgroups. Bleeding rates were also similar between treatments for BMI subgroups. Conclusions: Dabigatran is an effective thromboprophylactic therapy for normal, pre-obese and obese patients, and outcomes in patients with a BMI >25kg/m2 do not differ from the overall population. [Copyright &y& Elsevier]

After heart transplantation primary graft failure is a major cause of early mortality. Treatment options include inotropes and mechanical assist devices. Developing better methods would impact on patients’ short- and long-term survival. We present a case of primary graft failure manifested as cardiogenic shock unresponsive to catecholamines and a phosphodiesterase inhibitor. Reversal of low output syndrome was achieved with a new type of inotropic agent, levosimendan, leading to the later complete recovery. [Copyright &y& Elsevier]

Cognitive recovery after anaesthesia and surgery is a concern for older adults, their families, and caregivers. Reports of patients who were 'never the same' prompted a scientific inquiry into the nature of what patients have experienced. In June 2018, the ASA Brain Health Initiative held a summit to discuss the state of the science on perioperative cognition, and to create an implementation plan for patients and providers leveraging the current evidence. This group included representatives from the AARP (formerly the American Association of Retired Persons), American College of Surgeons, American Heart Association, and Alzheimer's Association Perioperative Cognition and Delirium Professional Interest Area. This paper summarises the state of the relevant clinical science, including risk factors, identification and diagnosis, prognosis, disparities, outcomes, and treatment of perioperative neurocognitive disorders. Finally, we discuss gaps in current knowledge with suggestions for future directions and opportunities for clinical and translational projects. [ABSTRACT FROM AUTHOR]

The oral direct thrombin inhibitor (oral DTI) ximelagatran (Exanta™, AstraZeneca) is rapidly absorbed and bioconverted to its active form melagatran, which also can be administered subcutaneously (sc). Two large-scale clinical trials (MElagatran for THRombin inhibition in Orthopaedic surgery [METHRO] II and III) have evaluated the safety and efficacy of sc melagatran followed by oral ximelagatran compared with low-molecular-weight heparins (LMWH) for thromboprophylaxis following total hip (THR) and total knee replacement (TKR) surgery. In METHRO II, patients received either 5000 IU sc dalteparin once daily (od) or a combination of one of four doses (from 1 to 3 mg) of sc melagatran twice daily (bid) started immediately before surgery, followed by one of four doses (from 8 to 24 mg) of oral ximelagatran bid started 1–3 days after surgery. In METHRO III, patients were randomized to receive either 40 mg sc enoxaparin od or 3 mg sc melagatran bid started 4–12 h after surgery followed by 24 mg oral ximelagatran. In METHRO II, there was a highly significant dose–response relationship for sc melagatran plus oral ximelagatran, with the highest dose combination superior to dalteparin in the prevention of venous thromboembolism (VTE). In METHRO III, a dosing regimen in which sc melagatran was started postoperatively and followed by oral ximelagatran was not more effective than enoxaparin started preoperatively. Thus, the time interval between surgery and the first dose of anticoagulant may be important in ensuring optimal efficacy. The METHRO II and III studies demonstrate that sc melagatran combined with oral ximelagatran are well tolerated and effective for the prevention of VTE following major orthopaedic surgery. [Copyright &y& Elsevier]

Background: Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function.Methods: In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid β (Aβ1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery.Results: CSF and blood concentrations of T-tau, neurone-specific enolase, and Aβ1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aβ1-42.Conclusions: The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction. [ABSTRACT FROM AUTHOR]

Background: The molecular actions underlying the clinical effects of inhaled anaesthetics such as sevoflurane and isoflurane are not fully understood. Unexpected observations in positron emission tomography (PET) studies with [11C]AZD9272, a metabotropic glutamate receptor 5 (mGluR5) radioligand with possible affinity for monoamine oxidase-B (MAO-B), suggest that its binding is sensitive to anaesthesia with sevoflurane. The objective of the present study was to assess the effects of sevoflurane anaesthesia on the binding of [11C]AZD9272 and of [11C]L-deprenyl-D2, a radioligand selective for MAO-B in non-human primates (NHPs).Methods: Altogether, 12 PET measurements were conducted with a high-resolution research tomograph using the ligands [11C]AZD9272 or [11C]L-deprenyl-D2 in six cynomolgus monkeys anaesthetised with sevoflurane or ketamine/xylazine.Results: The specific binding of [11C]AZD9272 and [11C]L-deprenyl-D2 was markedly reduced during anaesthesia with sevoflurane compared with ketamine/xylazine. The reduction was 80-90% (n=3) for [11C]AZD9272 and 77-80% (n=3) for [11C]L-deprenyl-D2.Conclusions: Sevoflurane anaesthesia inhibited radioligand binding to MAO-B in the primate brain. The observation of lower MAO-B binding at clinically relevant concentrations of sevoflurane warrants further exploration of the potential role of MAO-B related mechanisms in regulation of systemic blood pressure during anaesthesia. [ABSTRACT FROM AUTHOR]

With steadily shrinking areas of species-rich semi-natural grasslands in Europe, the management of the remaining fragments becomes ever more crucial for the preservation of key elements of biodiversity in the agricultural landscape. Detailed knowledge about species-wise, as well as group-wise, relationships can provide guidelines for conservation management and a basis for predictions about different management scenarios. In the present study, we related the occurrence of species of bumblebees (N = 12), butterflies (31) and day-flying moths (4) and their total richness in 424 sites in southern Sweden to three grass sward attributes, (i) flower abundance, (ii) height of the grass sward and (iii) within-site variation in height of vegetation. The abundance of nectar-bearing flowers proved overall the best predictor of richness and in most of the occurrence-based species-wise models. However, both high grass sward height and high variation in grass sward height contributed significantly to species richness and occurrence of individual species. There was a tendency for bumblebees to respond less positively to flower abundance and vegetation height than butterflies and moths. One expectation was that grassland specialists, red-listed species, or species decreasing in other part of Europe, would be more responsive to tall vegetation or flower abundance but there was no support for this in the data. Hence, management strategies that promote common species will also benefit all, or most of, the rare ones as well. [ABSTRACT FROM AUTHOR]

Background Major orthopaedic surgery involves a calculated risk of bleeding. In other groups of surgical patients, low preoperative plasma fibrinogen concentration and factor XIII (FXIII) activity have been associated with an elevated risk of bleeding. In the present study we investigated the association between preoperative fibrinogen plasma concentration and FXIII activity on bleeding and transfusion requirements in patients undergoing a spinal fusion procedure or hip or knee arthroplasty. Methods Two hundred and forty-five adult patients undergoing spine fusion surgery (n = 52), total unilateral primary hip arthroplasty (n = 114), or total knee arthroplasty (n = 79) were included in a prospective observational study. Blood samples were collected < 24 h before surgery and analysed for fibrinogen concentration and FXIII activity. Intraoperative and postoperative bleeding volume and transfusion requirements were recorded. Results Spinal fusion surgery patients with a low preoperative fibrinogen concentration (≤ 2.5 g/L) had a greater total perioperative median bleeding volume than patients with fibrinogen > 2.5 g/L (2430 (400–6560) mL vs. 1390 (400–7420) mL, p = 0.029). No significant association between low fibrinogen levels and perioperative bleeding volume was observed for arthroplasty patients. There was no association between low fibrinogen levels and transfusion requirements in any of the groups. Low FXIII activity was not significantly associated with bleeding volume and transfusion requirements in any group. Conclusion Measurement of preoperative fibrinogen plasma concentration can identify spinal fusion patients with an increased risk of excessive perioperative bleeding. Measurement of FXIII activity cannot identify orthopaedic patients with elevated risk of bleeding. [ABSTRACT FROM AUTHOR]

Elderly patients who have an acute illness or who undergo surgery often experience cognitive decline. The pathophysiologic mechanisms that cause neurodegeneration resulting in cognitive decline, including protein deposition and neuroinflammation, also play a role in animal models of surgery-induced cognitive decline. With the aging of the population, surgical candidates of advanced age with underlying neurodegeneration are encountered more often, raising concerns that, in patients with this combination, cognitive function will precipitously decline postoperatively. This special article is based on a symposium that the University of California, San Francisco, convened to explore the contributions of surgery and anesthesia to the development of cognitive decline in the aged patient. A road map to further elucidate the mechanisms, diagnosis, risk factors, mitigation, and treatment of postoperative cognitive decline in the elderly is provided. [ABSTRACT FROM AUTHOR]

Abstract: Propofol is a commonly used anesthetic agent, and it attenuates hypoxic ventilatory response in humans. Propofol reduce in vivo and in vitro carotid body responses to hypoxia as well as to nicotine in experimental animals. In the present study we examined the effects of propofol on carotid body responses to hypercapnia and K+-induced carotid body activation and compared these effects with hypoxia in an in vitro rabbit carotid body preparation. Hypoxia, hypercapnia and potassium increased the carotid sinus nerve activity and propofol attenuated the chemoreceptor responses to all three stimuli. However, the magnitude of propofol-induced attenuation was greater for hypercapnic and K+-induced carotid body activation compared to the hypoxic response. These observations suggest that propofol-induced attenuation of the hypoxic response is partly secondary to depression of chemoreceptor response to hypercapnia inhibiting the synergistic interactions between O2 and CO2 and may involve CO2/H+ sensitive K+ channels. [Copyright &y& Elsevier]

Neuromuscular blocking agents predominantly block muscle type nicotinic acetylcholine receptors as opposed to the neuronal type. However, there is growing evidence that neuromuscular blocking agents have affinity to some neuronal nicotinic acetylcholine receptors. The carotid body chemoreceptor as the essential oxygen-sensing cell, relies on cholinergic signalling. Atracurium and vecuronium impair carotid body chemoreceptor activity during hypoxia. Here, we characterize atracurium and vecuronium as antagonists at nicotinic receptors of the carotid body chemoreceptor. Isolated rabbit carotid body preparations with carotid sinus nerve were used, and chemoreceptor activities were recorded. There was a concentration-dependent reduction in the chemoreceptor responses to nicotine, with an IC50 to 50 μg nicotine of 3.64 and 1.64 μM and to 500 μg nicotine of 27.00 μM and 7.29 μM for atracurium and vecuronium, respectively. It is concluded that atracurium and vecuronium depress nicotine-induced chemoreceptor responses of the carotid body in a dose-dependent fashion. [Copyright &y& Elsevier]